UW-Madison School of Pharmacy

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Warren Heideman, Ph.D.

Professor


 

 

 


Cell Cycle Regulation. We are working to understand how yeast regulate the cell cycle in response to external signals. Cell cycle regulation is an important process in that improper cell cycle regulation can lead to cancer. It is also an important in biology because organized regulation of proliferative growth is a fundamental requirement for an organism, and absolutely required for the proper development of muticellular structures. More specifically, we are studying the connections between external signals and the conserved cyclin/cyclin dependent kinase (CDK) pathway that is thought to regulate progress from the G1 phase of the cell cycle into S phase. Yeast have proteins that are homologs to the products of the human p21ras oncogenes that are associated with many cancers. In yeast, the mitogen signal that regulates Ras is glucose. We are interested in how signals that control proliferation in yeast are coupled through Ras activity to the machinery of the cell cycle. Recently, we have identified Cln3, a G1 cyclin, as a major target for the Ras/cAMP pathway in yeast. We are also studying the transcriptional regulation of a number of yeast cell cycle genes to better understand how signals that produce proliferation in yeast control movement from G1 to S phase.

Developmental Toxicology. We are interested in studying the molecular mechanisms by which TCDD (dioxin) disrupts the normal developmental programing of fish. TCDD is a widespread environmental toxicant that accumulates in the food chain. TCDD activates a transcription factor, the arylhydrocarbon receptor (AhR) that in turn alters the pattern of gene expression. While it is assumed that alterations in gene expression lead to the toxic effects, it is not known what genes are critical in this response. Early life stage fish are more sensitive to TCDD than any other known organism. Because of their well known utility in genetic and developmental studies, we have established the zebrafish as a model system for studying this toxicity. In an attempt to identify genes that play a role in TCDD toxicity, we have initiated a selection for zebrafish mutants that are resistant to TCDD lethality.

Background: Warren received B.A. degrees in Zoology and Chemistry (1977), and a Ph.D. degree (1983) in Pharmacology from the University of Washington. He did postdoctoral work in the Department of Microbiology and Immunology at the University of California-Berkeley, and in the Department of Pharmacology at the University of California-San Francisco before joining the U.W. School of Pharmacy faculty in 1988. He holds faculty appointments in Biomolecular Chemistry, Molecular & Cellular Pharmacology, and Environmental Toxicology. He is also a Leukemia Society Fellow. His research interests center around signal transduction across biological membranes.

Professional Interests: Signal transduction across biological membranes

Education:

  • B.A. 1977 Zoology & Chemistry - University of Washington
  • Ph.D. 1983 Pharmacology - University of Washington
  • Postdoctoral Microbiology/Immun. - University of California-Berkeley
  • Postdoctoral Pharmacology - University of California-San Francisco
Highlighted Publications:
  • FR Burns, RE Peterson, and W Heideman.  Dioxin disrupts cranial cartilage and dermal bone development in zebrafish larvae.  Aquat Toxicol. 2015 Jul; 164:52-60.
  • MS Yue, RE Peterson, and W Heideman.  Dioxin inhibition of swim bladder development in zebrafish: is it secondary to heart failure?  Aquat Toxicol. 2015 May;162:10-7.
  • TR Baker, TC King-Heiden, RE Peterson, and W Heideman.  Dioxin induction of transgenerational inheritance of disease in zebrafish.  Mol Cell Endocrinol. 2014 Dec;398(1-2):36-41.
  • KA Lanham, J Plavicki, RE Peterson, and W Heideman.  Cardiac myocyte-specific AHR activation phenocopies TCDD-induced toxicity in zebrafish.  Toxicol Sci. 2014 Sep; 141(1)141-54.
  • JS Plavicki, P Hofsteen, MS Yue, KA Lanham, RE Peterson, and W Heideman.  Multiple modes of proepicardial cell migration require heartbeat.  BMC Dev Biol. 2014 May 15;14:18.
  • TR Baker, RE Peterson, and W Heideman.  Using zebrafish as a model system for studying the transgenerational effects of dioxin.  Toxicol Sci. 2014 Apr;138(2):403-11.
  • JS Plavicki, TR Baker, FR Burns, KM Xiong, AJ Gooding, P Hofsteen, RE Peterson, and W Heideman.  Construction and characterization of a sox9b transgenic reporter line.  Int J Dev Biol. 2014;58(9):693-9.
  • P Hofsteen, J Plavicki, RE Peterson, and W Heideman.  Epicardium Formation as a Sensor in Toxicology.  J Dev Biol. 2013 Jul 24;1(2):112-25.
  • PN Wiecinski, KM Metz, TC King Heiden, KM Louis, AN Mangham, RJ Hamers, W Heideman, RE Peterson, and JA Pedersen.  Toxicity of oxidatively degraded quantum dots to developing zebrafish (Danio rerio).  Environ Sci Technol. 2013 Aug 20;47(16):9132-9.
  • TR Baker, RE Peterson, and W Heideman.  Early dioxin exposure causes toxic effects in adult zebrafish.  Toxicol Sci. 2013 Sep;135(1):241-50.
  • P Hofsteen, J Plavicki, SD Johnson, RE Peterson, and W Heideman.  Sox9b is required for epicardium formation and plays a role in TCDD-induced heart malformation in zebrafish.  Mol Pharmacol.  2013 Sep;84(3):353-60.
  • J Zhang, KA Lanham, W Heideman, RE Peterson, and L Li.  Statistically enhanced spectral counting approach to TCDD cardiac toxicity in the adult zebrafish heart.  J Proteome Res. 2013 Jul 5;12(7):3093-103.
  • J Zhang, KA Lanham, W Heideman, RE Peterson, and L Li.  Characterization of zebrafish cardiac proteome using online pH gradient SCX-RP HPLC-MS/MS platform.  Methods Mol. Biol. 2013; 1005:119-27.
  • O Bar-Ilan, CC Chuang, DJ Schwahn, S Yang, S Joshi, JA Pedersen, RJ Hamers, RE Peterson, and W Heideman.  TiO2 nanoparticle exposure and illumination during zebrafish development:  mortality at parts per billion concentrations.  Environ Sci Technol.  2013 May 7;47(9)4726-33.
  • SP Yang, O Bar-Ilan, RE Peterson, W Heideman, RJ Hamers, and JA Pedersen.  Influence of humic acid on titanium dioxide nanoparticle toxicity to developing zebrafish.  Environ Sci Technol.  2013 May 7;47(9):4718-25.
  • P Hofsteen, V Mehta, MS Kim, RE Peterson, and W Heideman.  TCDD inhibits heart regeneration in adult zebrafish.  Toxicol Sci. 2013 Mar;132(1):211-21.
  • J Plavicki, P Hofsteen, RE Peterson, and W Heideman.  Dioxin inhibits zebrafish epicardium and proepicardium development.  Toxicol Sci.  2013 Feb; 131(2):558-67.
  • MK Conway, D Grunwald, and W Heideman.  Glucose, nitrogen, and phosphate repletion in Saccharomyces cerevisiae:  common transcriptional responses to different nutrient signals.  G3 (Bethesda).  2012 Sep;2(9):1003-17.
  • KA Lanham, RE Petesron, and W Heideman.  Sensitivity to dioxin decreases as zebrafish mature.  Toxicol Sci. 2012 Jun; 127(2): 360-70.
  • KA Lanham, AL Prasch, RE Peterson, and W Heideman.  A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity.  PLoS One 2011;6(12); e28020.  doi:  10.1371/journal.pone.0028020. Epub 2011.  Dec 15.